Method to generate novel bioactive molecules

摘要

The present invention describes a method to generate new chemical entities (NCEs) that have well-defined activities such as, but not limited to, anti-bacterial, antifungal and anthelmintic effects. The NCEs are generated through adaptive evolution of one microbe (the producer) against another organism or cell type (the target). The producer is made to compete against the target over time by co-culturing the two together and serially passing the producer organism until the producer adaptively evolves by synthesizing an NCE(s) that inhibits growth of or kills the target. The molecular structure of the chemical entity (or entities) is then elucidated using tools from genomics, molecular biology, computational biology, analytical chemistry, organic chemistry and related fields.

主权项

1. A method for identifying a bioactive compound in a culture comprising:
(i) co-culturing two or more organisms, wherein at least one organism is a parent producer organism and at least one other organism is a target and wherein the parent producer organism is Streptomyces clavuligerus and produces holomycin; (ii) detecting inhibition of growth of the target organism(s); (iii) isolating from the co-culture the parent producer organism after the detecting of OD; (iv) repeating (i)-(iii) at least once with the isolated producer and the target to produce an evolved strain of the parent producer, wherein the evolved strain may or may not produce holomycin; and (v) detecting the presence of one or more bioactive compounds in the co-culture in addition to or other than holomycin, thereby identifying a bioactive compound produced by the evolved producer organism.